Endocrine Abstracts

In patients with longstanding type 1 diabetes β-cell regeneration or β-cell replacement are the only options that result in normoglycemia without the risk of hypoglycemia. Although persistent C-peptide is present in ~10% of patients with type 1 diabetes, currently regeneration of eutopic pancreatic islets remains elusive due to the minimal regenerative capacity of the human pancreas and the presence of persistent autoreactivity. Islet transplantation is a form of β-cell replacement therapy that is a treatment option for a specific group of patients with type 1 diabetes that suffers from glycemic lability, recurrent hypoglycemic episodes and hypoglycemia unawareness. The minimally invasive nature of percutaneous intraportal infusion of isolated islets from human donor pancreas makes the procedure attractive compared to pancreas transplantation. There is only a small risk of portal vein thrombosis or hepatic bleeding. However, usually islet infusions from 2 to 3 donors are necessary to obtain insulin independence in islet transplant recipients. This is mostly related to the loss of islets during transplantation and islet engraftment. Although insulin independence may not be achieved after one islet infusion, partial islet graft function already leads to a substantial improvement in hypoglycemia-related problems. Over time islet graft function declines probably due to a combination of factors involving a suboptimal liver microenvironment for long-term islet function, impaired vascularisation, alloreactivity, recurrent autoreactity and toxic effects of immunosuppressive agents. So a substantial number of transplant recipients that once were insulin-independent after islet transplantation have to resume insulin therapy but continue to benefit from partial graft function. This has resulted in most islet transplantation centers now regarding an absence of severe hypoglycemic episodes and return of hypoglycemia awareness as indicators of successful islet transplantation.